Background
The effects of acute and repeated treatment with desipramine on the functional response of alpha2-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an alpha2-adrenoceptor agonist. The change in the extent of the brimonidine-induced hypothermia following pretreatment with either single or 4 twice-daily injections of desipramine was compared in 13-day old and adult (65-75 days old) male rats.
Conclusion
The results suggest that juvenile rats response differently than adult rats to agonist stimulation of alpha2-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the alpha2-adrenoceptor-induced hypothermic effect in juvenile rats is greater than in adult rats. Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats. In addition, the increased alpha2-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.
Results
Brimonidine, alone, lowered rectal temperature to a greater extent in juvenile than in adult rats, and this response was dose-dependently blocked by the selective alpha2-adrenoceptor antagonist, RX821002, in both groups of rats. Single desipramine administration lowered rectal temperature in the absence of brimonidine in adult but not in juvenile rats. The adult rats developed tolerance to this hypothermic effect after 4 days of desipramine treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.